Project description:Stress plays a role in tumourigenesis through catecholamines acting at β-adrenoceptors including β1 -, β2 - and β3 -adrenoceptors, and the use of β-adrenoceptor antagonists seems to counteract tumour growth and progression. Preclinical evidence and meta-analysis data demonstrate that melanoma shows a positive response to β-adrenoceptor blockers and in particular to propranolol acting mainly at β1 - and β2 -adrenoceptors. Although evidence suggesting that β3 -adrenoceptors may play a role as a therapeutic target in infantile haemangiomas has been recently reviewed, a comprehensive analysis of the data available from preclinical studies supporting a possible role of β3 -adrenoceptors in melanoma was not available. Here, we review data from the literature demonstrating that propranolol may be effective at counteracting melanoma growth, and we provide preclinical evidence that β3 -adrenoceptors may also play a role in the pathophysiology of melanoma, thus opening the door for further clinical assays trying to explore β3 -adrenoceptor blockers as novel alternatives for its treatment. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

| S-EPMC6592869 | biostudies-literature

Don't forget astrocytes when targeting Alzheimer's disease.

Project description:Astrocytes are essential for CNS health, regulating homeostasis, metabolism, and synaptic transmission. In addition to these and many other physiological roles, the pathological impact of astrocytes ("reactive astrocytes") in acute trauma and chronic disease like Alzheimer's disease (AD) is well established. Growing evidence supports a fundamental and active role of astrocytes in multiple neurodegenerative diseases. With a growing interest in normal astrocyte biology, and countless studies on changes in astrocyte function in the context of disease, it may be a surprise that no therapies exist incorporating astrocytes as key targets. Here, we examine unintentional effects of current AD therapies on astrocyte function and theorize how astrocytes may be intentionally targeted for more efficacious therapeutic outcomes. Given their integral role in normal neuronal functioning, incorporating astrocytes as key criteria for AD drug development can only lead to more effective therapies for the millions of AD sufferers worldwide. LINKED ARTICLES: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

| S-EPMC6715613 | biostudies-literature

Albumin Substitution in Decompensated Liver Cirrhosis: Don't Forget Zinc.

Project description:Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2-4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.

| S-EPMC8618355 | biostudies-literature

Patient Registries in Idiopathic Pulmonary Fibrosis: Don't Forget Socioeconomic Status.

Project description: Not available

| S-EPMC7159425 | biostudies-literature

Stem cell therapy for white matter disorders: don't forget the microenvironment!

Project description:White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in rodent disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.

| S-EPMC4920834 | biostudies-literature

Corticosteroids for dengue - why don't they work?

Project description:BackgroundDysregulated immune responses may contribute to the clinical complications that occur in some patients with dengue.FindingsIn Vietnamese pediatric dengue cases randomized to early prednisolone therapy, 81 gene-transcripts (0.2% of the 47,231 evaluated) were differentially abundant in whole-blood between high-dose (2 mg/kg) prednisolone and placebo-treated patients two days after commencing therapy. Prominent among the 81 transcripts were those associated with T and NK cell cytolytic functions. Additionally, prednisolone therapy was not associated with changes in plasma cytokine levels.ConclusionThe inability of prednisolone treatment to markedly attenuate the host immune response is instructive for planning future therapeutic strategies for dengue.

| S-EPMC3861232 | biostudies-literature

Post-SARS-CoV-2 vaccination acute hemolysis in an older man: don't forget to look at the blood smear.

Project description: Not available

| S-EPMC8614065 | biostudies-literature